Regulation of small GTPase activity by G1 cyclins

Together with a cyclin-dependent kinase (CDK) partner G1 cyclins control cell cycle entry by phosphorylating a number of nuclear targets and releasing a transcriptional program at the end of G1 phase. Yeast G1 cyclins also operate on cytoplasmic targets involved in the polarization of the cytoskeleton and vesicle trafficking. These processes are mainly controlled by the small GTPase Cdc42, and G1 cyclins regulate the activity of this and other small GTPases through the modulation of their regulators and effectors. This regulation is key for different developmental outcomes in unicellular organisms. In mammalian cells cytoplasmic G1 cyclin D1 has been shown to promote the activity of Rac1 and Ral GTPases and to block RhoA. Regulation of these small GTPases by G1 cyclins may constitute a mechanism to coordinate proliferation with cell migration and morphogenesis, important processes not only during normal development and organogenesis but also for tumor formation and metastasis. Here we briefly review the evidence supporting a role of G1 cyclins and CDKs as regulators of the activity of small GTPases, emphasizing their functional relevance both in budding yeast and in mammalian cells.This work was funded by Spanish Ministry of Education and Science (BFU2013-42895) from the Spanish Ministry of Economy and Competitivity and Catalan Government (SGR-559). T. Cemeli and MV Monserrat were supported by predoctoral fellowships from Spanish Ministry of Education and Science (FPU) and from University of Lleida, respectively

Genotoxicity and cytotoxicity of zinc oxide and titanium dioxide in HEp-2 cells.

yesAims: The rapidly growing industrial and medical use of nanomaterials, especially zinc oxide and titanium dioxide, has led to growing concerns about their toxicity. Accordingly, the intrinsic genotoxic and cytotoxic potential of these nanoparticles have been evaluated. Materials & methods: Using a HEp-2 cell line, cytotoxicity was tested along with mitochondrial activity and neutral red uptake assays. The genotoxic potential was determined using the Comet and the cytokinesis-blocked micronucleus assays. In addition,tyrosine phosphorylation events were investigated. Results & conclusion: We found concentration- and time-dependent cytotoxicity and an increase in DNA and cytogenetic damage with increasing nanoparticle concentrations. Mainly for zinc oxide, genotoxicity was clearly associated with an increase in tyrosine phosphorylation. Our results suggest that both types of nanoparticles can be genotoxic over a range of concentrations without being cytotoxic.Embargo ended 3/11/ 201

Characterization of cytoplasmic cyclin D1 as a marker of invasiveness in cancer

Cyclin D1 (Ccnd1) is a proto-oncogen amplified in many different cancers and nuclear accumulation of Ccnd1 is a characteristic of tumor cells. Ccnd1 activates the transcription of a large set of genes involved in cell cycle progress and proliferation. However, Ccnd1 also targets cytoplasmic proteins involved in the regulation of cell migration and invasion. In this work, we have analyzed by immunohistochemistry the localization of Ccnd1 in endometrial, breast, prostate and colon carcinomas with different types of invasion. The number of cells displaying membranous or cytoplasmic Ccnd1 was significantly higher in peripheral cells than in inner cells in both collective and pushing invasion patterns of endometrial carcinoma, and in collective invasion pattern of colon carcinoma. Also, the cytoplasmic localization of Ccnd1 was higher when tumors infiltrated as single cells, budding or small clusters of cells. To evaluate cytoplasmic function of cyclin D1, we have built a variant (Ccnd1-CAAX) that remains attached to the cell membrane therefore sequestering this cyclin in the cytoplasm. Tumor cells harboring Ccnd1-CAAX showed high levels of invasiveness and metastatic potential compared to those containing the wild type allele of Ccnd1. However, Ccnd1- CAAX expression did not alter proliferative rates of tumor cells. We hypothesize that the role of Ccnd1 in the cytoplasm is mainly associated with the invasive capability of tumor cells. Moreover, we propose that subcellular localization of Ccnd1 is an interesting guideline to measure cancer outcome.This work was funded by Spanish Ministry of Education and Science (BFU2010-20293/ BMC and BFU2013-42895-P), Catalan Government (SGR-559), and Fondo de Investigaciones Sanitarias (PI10/00604 and PI13/00263). X.M-G was supported by grants 2014SGR138, RD12/0036/0013, and Fundación Asociación Española contra el Cancer. Tumour samples were obtained with the support of Xarxa Catalana de Bancs de Tumors, and Plataforma de Biobancos ISCIII (PT13/0010/0014). NP. Fusté was supported by a contract from “Fundació Alicia Cuello de Merigó”. I. Felip and T. Cemeli were supported by a predoctoral fellowship from FPU-MINECO

Genotoxic and antigenotoxic properties of selenium compounds in the in vitro

Selenium is known to possess both genotoxic and antigenotoxic properties. In the present study, we have evaluated the genotoxicity and antigenotoxicity of three selenium compounds (sodium selenate, sodium selenite and selenous acid) by measuring in vitro micronucleus induction. Assays were conducted in whole blood lymphocytes and in the TK6 lymphoblastoid cell line, with and without co-treatment with potassium dichromate, a known genotoxic compound. In general, the compounds were more active in TK6 cells than they were in blood lymphocytes. Only 1 μM selenous acid increased the frequency of binucleated cells containing micronuclei (BNMN) in blood lymphocytes, while all three selenium compounds increased BNMN in TK6 cells. In addition, combinations of selenous acid and potassium dichromate resulted in lower frequencies of BNMN than potassium dichromate alone in blood lymphocytes, while combinations of sodium selenate and potassium dichromate produced lower frequencies of BNMN than potassium dichromate alone in TK6 cells. The concentrations of selenium compounds that were used, in combination with the medium components and the biological physiology of the whole blood lymphocytes and TK6 cells, could have affected the redox potential of the compounds, switching the chemicals from a pro-oxidant to antioxidant status and vice-versa. The lower activities of the compounds in blood lymphocytes may be due to the protective effects of blood components. The results indicate that the genotoxic and antigenotoxic properties of selenium compounds are highly dependent upon the conditions under which they are evaluated

Diseño e implementación de un juego de ajedrez P2E en el metaverso

El siguiente reporte documenta un proyecto que se presenta como TFG (Trabajo de Final de Grado) en la Facultad de Informática de Barcelona, que pertenece a la Universidad Politécnica de Cataluña. Concretamente forma parte de la especialidad de Sistemas de la Información. Se pretende diseñar e implementar un juego de ajedrez online dentro del metaverso de Decentraland, donde los jugadores podrán formar parte de diferentes modalidades de partidas compitiendo entre ellos.The following report documents a project presented as the Final Degree Project (TFG) at the Faculty of Informatics in Barcelona, affiliated with the Polytechnic University of Catalonia. Specifically, it is part of the Information Systems specialization. The aim is to design and implement an online chess game within the Decentraland metaverse, where players can engage in various gameplay modes and compete with each other

Assessment of Okadaic Acid Effects on Cytotoxicity, DNA Damage and DNA Repair in Human Cells

This is a manuscript version of the article.[Abstract] Okadaic acid (OA) is a phycotoxin produced by several types of dinoflagellates causing diarrheic shellfish poisoning (DSP) in humans. Symptoms induced by DSP toxins are mainly gastrointestinal, but the intoxication does not appear to be fatal. Despite this, this toxin presents a potential threat to human health even at concentrations too low to induce acute toxicity, since previous animal studies have shown that OA has very potent tumour promoting activity. However, its concrete action mechanism has not been described yet and the results reported with regard to OA cytotoxicity and genotoxicity are often contradictory. In the present study, the genotoxic and cytotoxic effects of OA on three different types of human cells (peripheral blood leukocytes, HepG2 hepatoma cells, and SHSY5Y neuroblastoma cells) were evaluated. Cells were treated with a range of OA concentrations in the presence and absence of S9 fraction, and MTT test and Comet assay were performed in order to evaluate cytotoxicity and genotoxicity, respectively. The possible effects of OA on DNA repair were also studied by means of the DNA repair competence assay, using bleomycin as DNA damage inductor. Treatment with OA in absence of S9 fraction induced not statistically significant decrease in cell viability and significant increase in DNA damage in all cell types at the highest concentrations investigated. However, only SHSY5Y cells showed OA induced genotoxic and cytotoxic effects in presence of S9 fraction. Furthermore, we found that OA can induce modulations in DNA repair processes when exposure was performed prior to BLM treatment, in co-exposure, or during the subsequent DNA repair process.This work was funded by a grant from the Xunta de Galicia (INCITE08PXIB106155PR). V. Valdiglesias was supported by a fellowship from the University of A CoruñaGalicia. Xunta; INCITE08PXIB106155P

La disfemia en el aula: propuesta de intervención desde una educación inclusiva

Entre los 2 y los 5 años de edad, los niños empiezan a constituir un lenguaje cada vez más elaborado. Este proceso en muchos niños supone la aparición de disfluencias normativas. Sin embargo, en algunos casos, estas alteraciones pueden perdurar y llegar a cronificarse como disfemia. A través de cuentos clásicos se presenta una propuesta de proyecto de intervención inclusiva para el segundo ciclo de educación infantil dentro de un aula ordinaria que orienta al docente y previene las manifestaciones tempranas de la tartamudez para evitar su cronificación y contribuye a mejorar las habilidades lingüísticas, emocionales el autoconcepto de todos y cada uno de los alumnos del grupo-clase. Además, se pone de relevancia tanto las actuaciones del maestro como las de la familia del alumno que presente alguna alteración en el habla en una edad normativa. La propuesta didáctica se agrupa en 5 bloques: relajación, emociones, valores, articulación y expresión oral que se refieren al trabajo en diferentes áreas como posibles causas de la disfemia, aunque su origen sea desconocido. En todas las sesiones se trabaja la narración de cuentos clásicos y se fomenta la expresión y escucha activa